While in Central City, Louisiana, orphans Andi (Emma Roberts) and Bruce (Jake T. Austin) manage to sell a rock in a box to a pawn shop to buy food for their dog, Friday (played by a dog named Cosmo), a Jack Russell Terrier. However, they are quickly caught and marched off to the police station, where their social worker, Bernie Wilkins (Don Cheadle) picks them up and takes them back to their foster parents, Lois and Carl Scudder (Lisa Kudrow and Kevin Dillon, respectively), who appear not to care for either Andi or Bruce. When the two demand to know where their foster children have been, Bernie covers for them, telling them that it was his fault they were late. Despite his sympathies towards the two siblings, he warns them that they are playing a dangerous game by deliberately getting into trouble in order to escape Carl and Lois, since they could get fostered separately, something that both orphans are desperate to avoid. During Bernie's visit, Friday returns home and Bruce quickly bustles Bernie out of the door, since Friday's presence is to be kept secret.

The next morning, Andi and Bruce are horrified to find that Friday has snuck inside and is dangerously close to Lois discovering him. After a close call, Andi and Bruce rush Friday back to their bedroom, where Friday promptly goes looking for food again, only to be caught by Animal Control. Sick with worry, Andi and Bruce go into a local pet shop to ask if anybody has seen him; there, they meet Dave, (Johnny Simmons) and Heather, (Kyla Pratt) who advise them to check the Pound. Upon learning that Friday is indeed in the Pound but they cannot claim him unless their parents are there, Andi pays for Friday's return instead and suggests to Bruce that they find Friday a new home, since he deserves a real home with a real family. Whilst walking home, they find a gang of youths having stolen a ghetto-blaster radio, only to flee before the police arrive. Andi and Bruce try to outrun the police (the same two who had caught them earlier) and manage to hide in a nearby abandoned hotel formerly known as "Hotel Francis Duke". Whilst looking for Friday, who had curiously begun to explore the hotel, they find a tiny Boston Terrier and an English Mastiff, whom they later name Georgia and Lenny, respectively. Confident that the three dogs are getting along, Andi and Bruce leave Friday at the hotel for the night.

The next morning, Andi and Bruce quickly return to the hotel to feed the dogs and to stop Lenny from getting caught due to howling because of lack of the city's view, with Andi warning her younger brother to not get too attached to the two stray dogs after naming them. Whilst Bruce stays at the hotel to keep the dogs quiet and creates a machine that allows them to play 'Fetch' whenever they like, Andi heads to the pet shop to get some food for the strays, claiming that her parents rescue dogs, prompting Dave to ask her to take in three more dogs - Shep: a Border Collie with herding issues, Romeo: a shy Chinese Crested Dog seeking romance, and Cooper: a British Bulldog with the ability to chew through anything (including a license plate) - who nobody seems to want to adopt since they aren't puppies anymore. Andi begrudgingly agrees. Upon arriving at the hotel, Dave and Heather immediately agree to help the two siblings out. With six dogs to now look after, the friends set about trying to get the hotel in a decent enough state to suit the dogs' needs, including building running machines, automatic feeders, modified lavatories, and a car simulator. Whilst they're working, a local boy named Mark offers his assistance. When Bruce brings in another dog: a Beauceron he found scrounging for food in a junkyard and which he named Henry, the group finally decides to set out and rescue more stray dogs from dog catchers, abusive owners, abandonment, certain death, former poor homes, bad conditions, and other types of bad situations. Soon, more strays begin to occupy the hotel. One of them, a white French Poodle, becomes Romeo's new love interest and is therefore named Juliet afterwards.

Back at the Scudder's household, Bernie eagerly tells them of a couple of new foster parents he's found for Andi and Bruce. However, their new foster parents live 3 hours away so, the two turn the offer down in order to continue looking after the dogs, much to Bernie's bewilderment. Whilst thinking over her decision, Dave invites Andi to a party and she happily accepts; Mark, meanwhile, makes various efforts to gain Heather's attention. Whilst everyone else is at the party, Bruce is caught stealing a hairdryer from Lois and is immediately interrogated by Lois and Carl; meanwhile, Andi bumps into an old acquaintance named Jason, who accidentally notifies everyone that Andi is an orphan living with the Scudders in the same building his grandmother lives in. After an accident with some Punch, Andi leaves in shame and embarrassment and Dave follows her. Bruce manages to escape his house, only to find the hotel in a bad state due to an automatic feeder malfunction and a dogfight over a bone, then, Andi arrives; Lois and Carl follow him and the police are called. Andi and Bruce round up the dogs and hide in a darkened room, but after one dog howls due to barely any light in the room, the dogs are quickly caught and sent to the Pound, while Bruce and Andi are taken away by officers Mike and Jeff. When Lois and Carl refuse to take Andi and Bruce back, Bernie has no choice but to send them to separate foster homes.

With all of the dogs to be put down the next day, Friday manages to escape his captivity and rushes over to find Dave, Heather, and Mark, who in turn find Andi. They all hurry over to find Bruce. Meanwhile, Bernie decides to look around the hotel, where he finds a Beagle named Coco who managed to avoid being caught the previous night, and marvels at the creations Bruce made, thus, begins to see why the kids loved doing what they did so much. Andi and Bruce manage to break into the Pound and release the dogs, where Bruce entices the horde of dogs to follow Dave's van through the city with sausages to a city limit where they can't be harmed while Mark stays behind to fight and hold off one of the dog catchers, who was trying to take Heather away to jail when he spotted her helping the siblings with their plan to rescue the dogs. The strange event attracts the attention of everyone in the city, including the police, who follow the dogs to the hotel after Friday leads them back when they realize that the hotel is their true home, where Bernie is waiting. With a large crowd gathered outside and before the cops try to take away the kids and the dog catchers try to capture the dogs again, Bernie shows up and tells the crowd a heartfelt speech about how Bruce, Andi, and everyone else managed to create a family of dogs and lists the names of the dogs and their former backstories (before being rescued) written in the hotel's old reception book by Bruce, who live at the hotel; winning the public's hearts, including the cops as well. The dog catchers are then called off, the pound is supposedly shut down, and the police, who always kept a close eye on the kids, allow to keep the dogs together.

As people eagerly explore the hotel and after Andi and Dave share a kiss, Bernie reveals to an overjoyed Andi and Bruce that despite not being able to find new foster parents, he and his wife Carol have decided to adopt them. Mark, having returned to the hotel, finally wins Heather's affections as he gratefully receives a kiss on the cheek by her as part of a baby step. A few months later, the hotel re-opens as a grand "Hotel For Dogs", where people can either adopt strays or board their dogs. Dave is made the new hotel manager while Heather is the new hotel guide. Lenny and Georgia (having supposedly pursued a romantic relationship with Henry) are a few of the dogs working as porters while Cooper works in the recycle bin as he chews off everything recyclable. The hotel also includes a nursery and care center, an adoption center, a beauty salon, and a spa. Although Lois and Carl are invited to provide the entertainment for the "Hound Lounge", the dogs quickly grow bored with their act and the two are supposedly sent offstage in disgrace. Meanwhile, Andi, Bruce, and Friday begin to happily settle into their new family as they have a barbecue lunch with their new foster parents on the hotel's terrace.

Jake T. Austin as Bruce, an orphan who, along with his older sister, Andi, has lived with a number of foster parents before ending up with Lois and Carl Scudder. He has a knack for mechanics. His inventions help keep the stray dogs living at the hotel fed and entertained while he and his sister are away. Nearly 80 boys tried out for the part before Austin was cast as Bruce.

Emma Roberts as Andi, Bruce's older sister. Roberts was cast in late 2007[4] and "knew as soon as soon as she started reading the script for Hotel for Dogs, she wanted to be part of the movie".[5]

Johnny Simmons as Dave, the young manager of a local pet store who helps Andi and Bruce rescue stray dogs and care for them at the hotel. Later, he becomes Andi's boyfriend and the new manager at the Hotel For Dogs.

Troy Gentile as Mark, a young kid who lives near Andi and Bruce and is eager to help with the dogs at the hotel. Later, he becomes Heather's boyfriend.

Kyla Pratt as Heather, an employee at the pet store who also wants to help rescue stray dogs and later, becomes the new guide at the Hotel For Dogs. Pratt joined the film after she learned that Don Cheadle was also working on the project. She said in an interview that "they were telling me about all the different people who were gonna be in it, and I saw Don Cheadle's name, and I'm like, oh, absolutely". She also said of her co-star Emma Roberts that "Emma is so much fun to be around and she's hilarious. Emma's great because I wasn't sure how everything was going to be, because I was older than the other actors in the movie".[6]

Don Cheadle as Bernie Wilkins, a sympathetic social worker who tries his best to find a home for Andi and Bruce and to prevent them from being placed with separate foster families. Later, he becomes Andi and Bruce's new foster father at the end. Cheadle joined the cast in September 2007.[7] He described the film as "an opportunity to do a film that my kids can see" and praised both Emma Roberts and Jake T. Austin as being "really professional. They showed up to do the work and were serious and took it seriously and had acting coaches and everything".[8]

Robinne Lee as Carol Wilkins, Bernie's wife who initially tells her husband not to get too emotionally involved with the children he works with despite showing deep sympathy and care for them as well. Later, she becomes Andi and Bruce's new foster mother.

Lisa Kudrow as Lois Scudder, Andi and Bruce's controlling, wannabe rock star foster mother. Kudrow signed up for the film in October 2007.[9] It was her first time working with dogs in a film. She said that her co-star Emma Roberts "was one of the draws for me to do this".[10]

Kevin Dillon as Carl Scudder, Andi and Bruce's foster father and an aging rocker who refuses to give up on his dreams of becoming a star. Dillon was cast in November 2007.[11] Dillon said in an interview that singing and playing guitar during the band practice scenes was "one of the things that was the most fun" while filming.[12]

Gregory Sporleder as ACO Herb Dooley; the chief and boss of the animal pound workers, who stops at nothing to capture stray dogs, put them in cages, and then, have them put to sleep.

Eric Edelstein as ACO Max; a morbidly obese, cruel, cold hearted animal pound worker, who along with his similar partner Jake, does everything in his power to lock up every stray dog in the city, even Andi and Bruce's own dog, Friday and probably other dogs with name tag collars on them.

Ajay Naidu as ACO Jake; a cruel, cold hearted animal worker, like his partner Max, who does everything in his power to lock up and put down every stray dog they find and capture in the city.

Maximiliano Hernández as Officer Mike; a strict, yet caring, police officer, who along with his partner Jeff, has been keeping an eye on Andi and Bruce since the time they ripped a pawn shop owner off. At the end, he allows Andi and Bruce to keep the dogs.

Andre Ware as Officer Jeff; Officer Mike's similar partner who has been keeping an eye on Andi and Bruce since the time they ripped a pawn shop owner off. At the end, he allows Andi and Bruce to keep the dogs as well.

Jonathan Klein as Evan; a pawn shop owner whom Andi ripped off by selling him a rock in a phone box for twenty-seven dollars at the beginning.

Kenny Vibert as Jason; an old acquaintance of Andi and Bruce, who accidentally notifies everyone that Andi is an orphan living with the Scudders in the same building his grandmother lives in at the party.

"It draws an interesting parallel between the kids and the dogs. Although I was aware that it was a risk to jump into directing my first feature working with both kids and animals, I recognized the importance and relevance of the story and thought it was worth it"

The film rights to Lois Duncan's novel were acquired by DreamWorks in June 2005.[14] According to Thor Freudenthal, DreamWorks first approached him about working on the film after a short film which he had worked on played at the Sundance Film Festival. Freudenthal said that DreamWorks "really embraced and responded to" the film and sent him an early version of the script. He was initially hesitant to sign onto the project, balking at the seemingly shallow title. However, he stated that after reading the script that he "realized you don’t think much about the logistics involved" and saw deeper messages and more complex aspects of the film.[15] Freudenthal was attracted to the "urban fairytale aspect" of the film, noting in an interview:

"It’s basically these unwanted children, these unwanted animals coming together and making their own place in their own home. That’s what I liked. It wasn’t the fact that it was Fox Terriers and things like that. So that sort of made me sign on and be ready for it."[15]

A producer of the film, Lauren Shuler Donner, is also an activist and dog lover, and was convinced that the book's message about the importance of family "made the novel an ideal property to bring to the big screen"[13] Shuler Donner insisted that the movie "stand out from other family movies visually" and it was Freudenthal's background in animation that gave him an edge over other directors. According to her, "It was the way he framed shots, the way he moved the camera, the use of color, the use of light. He’s very visually savvy and very specific."[13]

Emma Roberts was cast in August 2007 to play teenage older sister Andi. Freudenthal began his search for a young actress "who could carry a whole movie" and settled on then-16 year old Roberts. Ewan Leslie, a producer of the film, said in an interview of Roberts that she "is one of those young actors whose face just lights up the screen and she has the ability to play a wide range of emotions without any dialogue."[13]

Filmmakers conducted a nationwide search for an actor to play Bruce, Andi's whimsical and inventive younger brother. Jake T. Austin auditioned late, after nearly 80 other boys had tried out for the part. Jason Clark, another producer of the film, stated that Austin "was amazing on every level. He played the emotional beats very well, felt the role and also understood timing."[13]

The rest of the roles were cast in the following months. Don Cheadle, who plays Andi and Bruce's protective social worker, joined the film in September 2007. Lisa Kudrow was cast as the siblings' foster mother in October, and Johnny Simmons was cast that same month as Dave. Kyla Pratt was chosen to play Heather soon after.[13]

The dogs were carefully cast as well. Filmmakers wanted a variety of breeds with different colors and facial structures "so that their look suggested their personality."[13] Freudenthal said that he deliberately chose both very small and very large dogs to create a contrast similar to the characters of Lenny and George in the John SteinbecknovellaOf Mice And Men. The majority of the dogs cast were rescues. The lead dog, who plays Friday, was rescued about six months before shooting began. Crew members also helped to find adoptive homes for the abandoned dogs and several adopted dogs themselves.[13]

A Hollywood animal trainer, Mark Forbes, was hired to prepare the dogs before shooting began. Forbes and his team began working with the dogs about four months before shooting. Those dogs with no prior training were first taught basic commands, such as "sit" and "roll over." They were then trained to respond to more complex commands and learned to retrieve objects and to wave.

The dogs sit in replicas of cars surrounded by fans that simulate driving on a highway with the wind blowing.

The next phase of training involved using the dogs' body language to express emotions: sadness, for example, was conveyed when a dog tucked its tail between its legs. Finally, the dogs were taken to public places to review the commands that they had learned. The purpose of this was to ensure that the dogs would perform in any location. According to Forbes, "You want the dogs to sense that everything is fine and they’ll still get their treat regardless of the location. The set becomes just another place for them to go."[13] The trainers worked with the human actors as well to "familiarize them with how the dogs behave and create a comfort level between the human and the dog actors."[13] The dogs were also trained to interact with the various gadgets in the film with early prototypes built by the special effects team.

Special effects supervisor Michael Lantieri enlisted to create the various contraptions invented by Bruce throughout the film to keep the dogs fed. One such gadget is a device which can be operated by the dogs to throw a ball to be fetched.

"The first was a simple spring-loaded device that throws a ball and spoon down hallways, while the second device was a bit more sophisticated. 'This fetching machine uses a bicycle and a hand from a mannequin. It is timed so that the wheels turn, and the ball is magnetic so it sticks in the hand, which comes round and launches the object so the dog can chase it,' explains Lantieri. 'Things can seem simple when you read them, but making it work on screen has to do with timing, the weight of the ball and how the ball stays in the hand until you want it to move.'"[13]

Other devices built for the film include a feeding machine that drops food into each of the dogs' bowls on a timed schedule, a vending machine filled with shoes and other chew toys, a room filled with doors whose doorbells go off on their own, and another containing a replica of a car surrounded by fans which simulates for the dogs the experience of placing their heads through an open car window while driving.

All of the contraptions were created using objects that might actually be found in an abandoned hotel, and in such a way that they looked like they had been created by a gifted 13-year-old boy.

Hotel for Dogs was released in Puerto Rico on January 15, 2009, and in the United States on January 16, 2009, to 3,271 theaters. It earned $17,012,212 in its opening weekend,[16] the 5th-highest grossing film of that weekend behind Paul Blart: Mall Cop, Gran Torino, and others. It remained in release for 19 weeks and earned a total of $116,983,275 worldwide.[17] It is estimated to have earned $22,500,000 total over the four-day weekend.

Moviefone called the opening, "pretty good for a fairly anonymous little family film opening against a higher-profile family film."[18] As of August 2011, the film has a reported box office gross of $73,034,460 for the United States and $43,965,738 internationally, for a total of $117,000,198.[16]

The film received mixed reviews from critics. According to Rotten Tomatoes, a website which aggregates film reviews, 45% of critics gave Hotel for Dogs a positive review; the site's consensus further stated: "Hotel for Dogs may appeal to children and dog lovers, but it's ultimately contrived, predictable and simplistic".[19]Roger Ebert gave the film a 2.5 out of 4 stars and summed up his review by saying, "What I thought instead was, Marley has a lot he could learn from these dogs". Kent Turner, writing for School Library Journal, stated that while the book is "utterly realistic", the film is "fantastic" and thus fundamentally different.[20]Stephen Holden, writing for The New York Times, wrote that the film "is loaded with enough stupid pet and human tricks to satisfy David Letterman for years to come".[21]

The film was released to DVD on April 28, 2009. It sold 773,000 units in the first week, bringing in $13,584,527 in revenue. As per the latest figures, 1,778,736 DVD units have been sold, translating to more than $30 million in revenue.[22] This does not include Blu-ray sales.